There are many factors that affect blood pressure, including volume and salt content of body water, condition of the kidneys, nervous system, blood vessels, and various hormone levels. Baroreflexes are the major mechanism of blood pressure stabilization. One of the key observations in the reflex control of the circulation is that stimulation of the baroreflex pressure sensors, the baroreceptors, decreases blood pressure (Shoukas A A. Overall systems analysis of the carotid sinus baroreceptor reflex control of the circulation. Anesthesiology 79: 1402-1412, 1993). The major baroreceptors are located in the carotid sinus and the aortic arch; electrical stimulation of nerves from these areas is interpreted by the brain as an increase of blood pressure, and the brain activates compensatory (negative feedback) mechanisms, which, by increasing parasympathetic, and decreasing sympathetic activity, reduce blood pressure.
Since the mid 1960's, electrical stimulation of the carotid sinus nerve has been used to treat severe hypertension patients, who were resistant to medications (Schwartz S I, Griffith L S C, Neistadt A, et al.: Chronic carotid sinus nerve stimulation in the treatment of essential hypertension. Am J Surg 1967, 114: 5-15); (Schwartz S I: Clinical applications of carotid sinus nerve stimulation. Cardiovasc Clinl 1969, 1: 208-222). In these early studies, electrodes were attached directly to the carotid sinus nerve, and an implanted stimulator was used to continuously supply current pulses to the electrodes. Results from these early studies were promising, and suggested the possibility that prolonged baroreceptor nerve stimulation could generate sustained reductions in arterial pressure in hypertension patients. However, the baroreflex stimulation technologies have never become established; and these early efforts have never become clinically practical. One of the main factors that discouraged the establishment of the baroreflex stimulation technology was the dominance of the baroreflex resetting theory. In these early studies, continuous stimulation was used to produce sustained reductions in blood pressure. This strategy was logical from a conventional linear time invariant (LTI) control theory perspective; however, whether the baroreflex is, indeed, a “conventional” control system, was and still is, open to question. In fact, in the mid 50's, McCubbin et al. (McCubbin J W, Green J H, Page I H. Baroreceptor function in chronic renal hypertension. Circ Res. 1957; 4; 205-210) demonstrated a marked resetting of the arterial baroreflex in chronic hypertension, and since then there has been doubt, in cardiovascular medicine, as to whether the baroreflexes actually do participate in long-term control of arterial pressure (Cowley, A. W. Jr. Long-term control of the arterial blood pressure. Physiol Rev. 1992; 72: 231-300); (Lohmeier, T. E. The sympathetic nervous system and long-term blood pressure regulation. Am J Hypertens. 2001; 14: 147s-154s).
Irrespective of theoretical considerations, hypertension, or high blood pressure, remains among the most serious diseases contributing to morbidity and mortality in the US. Sustained hypertension can cause heart failure, stroke, kidney disease, and damage to many organs. Data from the National Health and Nutrition Examination Survey (NHANES) indicated that 50 million or more Americans suffer from high blood pressure (Burt V L, Whelton P, Roccella E J, Brown C, Cutler J A, Higgins M, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension 1995; 25; 305-13); (Hajjar I, Kotchen T A. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA 2003; 290: 199-206); estimates from the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), indicated that only 34% of the hypertensive population in the US is adequately controlled (Chobian A V, Bakris G L, Black H R, et al.: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Hypertension 2005, 42: 1026-1252). Among all patients with hypertension, at least 10% suffer from resistant hypertension, which is defined as failure to achieve a blood pressure of less than 150/90 mmHg, despite the use of a rational triple-drug regimen in optimal doses. Given such a high rate of pharmacologically intractable hypertension, it is clear that alternative treatment technologies are needed.
Thus, new methods are required for regulating blood pressure in individuals having hypertension or other blood pressure-related pathologies.